کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1911463 | 1046818 | 2007 | 8 صفحه PDF | دانلود رایگان |

Serum and tumor copper levels are significantly elevated in a variety of malignancies including breast, ovarian, gastric, lung, and leukemia. D-Penicillamine (D-pen), a copper-chelating agent, at low concentrations in the presence of copper generates concentration-dependent cytotoxic hydrogen peroxide (H2O2). The purpose of these studies was to investigate the in vitro cytotoxicity, intracellular reactive oxygen species (ROS) generation, and the reduction in intracellular thiol levels due to H2O2 and other ROS generated from copper-catalyzed D-pen oxidation in human breast cancer cells (BT474, MCF-7) and human leukemia cells (HL-60, HL-60/VCR, HL-60/ADR). D-pen (≤ 400 μM) in the presence of cupric sulfate (10 μM) resulted in concentration-dependent cytotoxicity. Catalase was able to completely protect the cells, substantiating the involvement of H2O2 in cancer cell cytotoxicity. A linear correlation between the D-pen concentration and the intracellular ROS generated was shown in both breast cancer and leukemia cells. D-pen in the presence of copper also resulted in a reduction in intracellular reduced thiol levels. The H2O2-mediated cytotoxicity was greater in leukemia cells compared to breast cancer cells. These results support the hypothesis that D-pen can be employed as a cytotoxic copper-chelating agent based on its ROS-generating ability.
Journal: Free Radical Biology and Medicine - Volume 43, Issue 9, 1 November 2007, Pages 1271–1278